Cardiac valve replacement using prosthetic valves is indicated when progression of degenerative disease, annular dilatation or bacterial infection of the native valve results in valvular dysfunction. Bacterial infection is a major complication associated with implantation of these prosthetic valves. Infections are localized to the biomaterial/tissue interface leading to cuff and annular abscess formation. In phase I, an infection-resistant knitted polyester (Dacron) cuff material was developed in vitro with optimum antimicrobial properties via thermofixation (pad/heat) dyeing of the antibiotic ciprofloxacin (Cipro). Application of this technology resulted in slow, sustained antibiotic release without the use of exogenous binders. The goal of this phase II project is to assess this novel infection-resistant knitted Dacron cuff material in vivo. Our hypothesis is that application of quinolone antibiotics such as Cipro to Dacron sewing cuffs using our proprietary dyeing technology will significantly reduce cardiac valve infections when challenged with a significant bacterial inoculum. The specific aims of this phase II proposal are to: 1) apply Cipro to clinically-utilized sewing cuffs using technology developed in phase I, 2) evaluate antimicrobial activity of Cipro-dyed sewing cuffs via zone of inhibition, 3) examine physical properties of Cipro-dyed Dacron sewing cuffs, 4) implant unmodified (clinical standard) and Cipro-dyed sewing cuffs in a porcine heart valve infection model, 5) assess control and Cipro-dyed Dacron sewing cuffs via histological/microbiological techniques and 6) determine physical properties of Cipro-dyed sewing cuffs post-explantation. This technology, if successful, will be become the standard of care in the treatment of all forms of prosthetic endocarditis and may have an annual market in excess of $25 million. This technology can be applied to other medical devices that are comprised of Dacron such as vascular grafts, carotid patch material, wound dressings and suture material. This technology may also have broad application in other industries requiring biomaterials with antimicrobial properties such as respirators, facemasks, veterinary medicine and other commercial ventures.